Mymetics Corp (MYMX)

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Winning by a nose
Despite the fact that many viruses initially enter the body through mucosal surfaces, most vaccines are administered by nonmucosal routes. This is, in part, due to historically poor development of immune responses after mucosal immunization. To address this, Hartwell et al. developed lipid-conjugated immunogens, called amph-proteins, and administered them intranasally to mice and nonhuman primates; these vaccines, which used the neonatal Fc receptor to mediate transmucosal uptake, elicited immune responses at both local and distal mucosal sites. These data support further development of amph-protein–based intranasal vaccines for immunogens such as the SARS-CoV-2 receptor binding domain and the HIV envelope protein, among others.
Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2–neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.

AffiliationsExpand All
Brittany L. Hartwell https://orcid.org/0000-0002-5438-9010
Mariane B. Melo https://orcid.org/0000-0002-0409-2454
Peng Xiao https://orcid.org/0000-0002-5308-8400
Ashley A. Lemnios
Na Li
Jason Y.H. Chang https://orcid.org/0000-0002-2238-8232
Jingyou Yu https://orcid.org/0000-0002-0775-6623
Makda S. Gebre https://orcid.org/0000-0001-8520-2178
Aiquan Chang https://orcid.org/0000-0002-9482-0979
Laura Maiorino https://orcid.org/0000-0001-8217-1337
Crystal Carter https://orcid.org/0000-0001-8929-3839
Tyson J. Moyer
Neil C. Dalvie https://orcid.org/0000-0002-7912-0309
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roles: Investigation, Resources, and Writing - review & editing.
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Sergio A. Rodriguez-Aponte https://orcid.org/0000-0002-6271-7918
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Role: Resources.
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Kristen A. Rodrigues https://orcid.org/0000-0002-0680-9834
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roles: Formal analysis, Investigation, Methodology, Resources, and Writing - review & editing.
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Murillo Silva https://orcid.org/0000-0003-4668-6290
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Roles: Investigation and Resources.
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Heikyung Suh
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roles: Methodology, Project administration, and Resources.
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Josetta Adams https://orcid.org/0000-0001-6416-2330
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roles: Formal analysis and Investigation.
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Jane Fontenot https://orcid.org/0000-0002-1846-7915
New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
Roles: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Supervision, and Validation.
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J. Christopher Love https://orcid.org/0000-0003-0921-3144
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Roles: Conceptualization, Project administration, Supervision, and Writing - review & editing.
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Dan H. Barouch https://orcid.org/0000-0001-5127-4659
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Roles: Data curation, Investigation, Project administration, Resources, and Supervision.
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Francois Villinger https://orcid.org/0000-0002-7790-2008
New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560 USA.
Roles: Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Validation, and Writing - review & editing.
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Ruth M. Ruprecht
New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
Roles: Funding acquisition, Project administration, and Supervision.
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Darrell J. Irvine* https://orcid.org/0000-0002-8637-1405 [e-mail]
Funding Information
National Institutes of Health: INV-004954
National Cancer Institute: P30-CA14051
National Institute of Allergy and Infectious Diseases: P01AI048240
National Institute of Allergy and Infectious Diseases: UM1AI144462
National Institute of Allergy and Infectious Diseases: P01AI048240
National Institute of Allergy and Infectious Diseases: P01AI048240
James S. McDonnell Foundation: 10.37717/220020569
U.S. Army Research Office: W911NF-18-2-0048

https://www.science.org/doi/epdf/10.1126/scitranslmed.abn1413
https://www.researchgate.net/publication/362145638_Intranasal_vaccination_with_lipid-conjugated_immunogens_promotes_antigen_transmucosal_uptake_to_drive_mucosal_and_systemic_immunity